The activity of internal organs is controlled by the autonomic nervous system. On p. 6635,Dauger et al. report that the transcription factor Phox2b is required for the differentiation of the afferent relays of autonomic reflexes. They show that the carotid body, a chemosensor organ, degenerates in Phox2b null mice, as do the cranial ganglia, which constitute the primary visceral sensory neurons. The central target of these neurons - the nucleus of the solitary tract, which integrates all visceral information - fails to form at all. These results help to establish Phox2b as a transcription factor required for the formation of autonomic reflex pathways. In addition, because mice heterozygous for Phox2b have respiratory defects similar to those seen in congenital central hypoventilation syndrome (which correlates with heterozygous mutations in PHOX2B), these results provide mechanistic insights into this human syndrome.